PARSIPPANY, NJ.--(BUSINESS WIRE)--Ferring Pharmaceuticals today announced the publication in the journal Drugs of its pivotal Phase 3 PUNCH™ CD3 clinical trial data, in which a single dose of RBX2660 demonstrated superiority to placebo as a treatment to reduce recurrence of Clostridioides difficile infection (CDI) after standard-of-care antibiotic treatment in a Bayesian analysis model. RBX2660 is an investigational microbiota-based live biotherapeutic studied for its potential to reduce recurrent CDI (rCDI) after antibiotic treatment.
In the randomized, double-blind, placebo-controlled trial, 267 participants – about a third of which were treated at first recurrence - received blinded treatment (n=180, RBX2660; n=67, placebo) and the primary endpoint was treatment success, defined as the absence of CDI diarrhea within eight weeks after completing study treatment. The model-estimated treatment success rate at eight weeks for RBX2660 was 70.6% versus 57.5% for placebo, with a 99.1% posterior probability that RBX2660 was superior to placebo in reducing rCDI after standard-of-care antibiotic treatment. More than 90% of study participants who achieved treatment success remained free of CDI recurrence through six months.
In the study, adverse events (AEs) were primarily mild-to-moderate and there were no treatment-related serious adverse events (SAEs). Incidence of treatment-emergent adverse events (TEAEs) was higher in RBX2660 recipients compared with placebo (55.6%, n=100/180, RBX2660; 44.8%, n=39/87, placebo), mostly driven by a higher incidence of mild gastrointestinal (GI) events.
“The findings from this Phase 3 trial provide hope that this potential treatment could make a meaningful difference in the lives of patients with recurrent C. difficile infection,” said Sahil Khanna, M.B.B.S, M.S., Mayo Clinic and lead researcher on the study.
The researchers used a Bayesian hierarchical model, developed in discussions with the U.S. Food and Drug Administration (FDA) and implemented prior to enrollment completion, data unblinding and analyses of study data, to conduct the efficacy analysis of the primary endpoint. This approach allowed borrowing of data from the previous Phase 2b study (PUNCH CD2) to augment patient enrollment for this orphan population and was appropriate due to similarity of the PUNCH CD2 and CD3 study designs.
The published manuscript, titled, “Efficacy and Safety of RBX2660 in PUNCH CD3, a Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial With a Bayesian Primary Analysis for the Prevention of Recurrent Clostridioides difficile Infection” is available online.
About C. difficile infection
C. difficile infection (CDI) is a serious and potentially deadly disease that impacts people across the globe. The C. difficile bacterium causes debilitating symptoms such as severe diarrhea, fever, stomach tenderness or pain, loss of appetite, nausea and colitis (an inflammation of the colon).1 Declared a public health threat by the U.S. Centers for Disease Control and Prevention (CDC) requiring urgent and immediate action, CDI causes an estimated half a million illnesses and tens of thousands of deaths in the U.S. alone each year.1,2,3
C. difficile infection often is the start of a vicious cycle of recurrence, causing a significant burden for patients and the healthcare system.4,5 It has been estimated that up to 35% of CDI cases recur after initial diagnosis and people who have had a recurrence are at significantly higher risk of further infections.6,7,8,9 After the first recurrence, it has been estimated that up to 65% of patients may develop a subsequent recurrence.8,9
RBX2660 is an investigational microbiota-based live biotherapeutic studied for its potential to reduce recurrence of C. difficile infection after antibiotic treatment. RBX2660 has been granted Orphan and Breakthrough Therapy designations from the U.S. Food and Drug Administration (FDA). RBX2660 was developed by Rebiotix, a Ferring company.
About the PUNCH™ CD3 Clinical Trial (Clinicaltrials.gov identifier: NCT03244644)
PUNCH CD3 is a Phase 3, prospective, multi-center, randomized, double-blinded, placebo-controlled clinical trial evaluating the efficacy and safety of RBX2660 vs. placebo in preventing rCDI. The study included adults ages 18 or older who had at least one recurrence after a primary episode of CDI who had completed one or more rounds of standard-of-care antibiotic therapy or had two or more episodes of severe CDI resulting in hospitalization within the past year. Participants were followed up to eight weeks for the primary efficacy analysis, and up to six months for efficacy and safety analyses. The TEAEs were mild-to-moderate GI symptoms in both the RBX2660 and placebo-treated arms.
About the PUNCH™ CD2 Clinical Trial (Clinicaltrials.gov identifier: NCT02299570)
PUNCH CD2 is a Phase 2b, randomized, double-blind, placebo-controlled trial, with data indicating the drug was well-tolerated and demonstrated statistically significant treatment efficacy. The study included adults ages 18 or older who had at least two recurrences of CDI after a primary episode or had completed at least two rounds of standard-of-care oral antibiotic therapy or have had at least two episodes of severe CDI resulting in hospitalization. Participants were followed up to eight weeks for the efficacy analysis, and up to 24 months for the safety analysis.
About Ferring Pharmaceuticals
Ferring Pharmaceuticals is a research-driven, specialty biopharmaceutical group committed to helping people around the world build families and live better lives. In the United States, Ferring is a leader in reproductive medicine and maternal health, and in specialty areas within gastroenterology and orthopaedics. For more information, call 1-888-FERRING + (1-888-337-7464); visit http://www.ferringusa.com/.
Ferring is committed to exploring the crucial link between the microbiome and human health, beginning with the threat of recurrent C. difficile infection. Ferring is working to develop novel microbiome-based therapeutics to address significant unmet needs and help people live better lives. Connect with us on our dedicated microbiome therapeutics development channels on Twitter and LinkedIn.
- Centers for Disease Control and Prevention. What Is C. Diff? 17 Dec. 2018. Available from: https://www.cdc.gov/cdiff/what-is.html
- Centers for Disease Control and Prevention. Biggest Threats and Data, 14 Nov. 2019. Available from: https://www.cdc.gov/drugresistance/biggest-threats.html
- Fitzpatrick F, Barbut F. Breaking the cycle of recurrent Clostridium difficile. Clin Microbiol Infect. 2012;18(suppl 6):2-4.
- Centers for Disease Control and Prevention. 24 June 2020. Available from: https://www.cdc.gov/drugresistance/pdf/threats-report/clostridioides-difficile-508.pdf
- Feuerstadt P, et al. J Med Econ. 2020;23(6):603-609.
- Riddle DJ, Dubberke ER. Clostridium difficile infection in the intensive care unit. Infect Dis Clin North Am. 2009;23(3):727-743.
- Nelson WW, et al. Health care resource utilization and costs of recurrent Clostridioides difficile infection in the elderly: a real-world claims analysis. J Manag Care Spec Pharm. 2021;27(7):828-838. doi: 10.18553/jmcp.2021.20395. Epub 2021 Mar 11.
- Kelly, CP. Can we identify patients at high risk of recurrent Clostridium difficile infection? Clin Microbiol Infect. 2012;18(suppl 6):21–27.
- Smits WK, et al. Clostridium difficile infection. Nat Rev Dis Primers. 2016;2:16020. doi: 10.1038/nrdp.2016.20.